| Project/Area Number |
16K11008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 義明 山口大学, 医学部附属病院, 助教 (30593298)
清木 誠 山口大学, 大学院医学系研究科, 教授 (50226619)
松山 豪泰 山口大学, 大学院医学系研究科, 教授 (70209667)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 去勢抵抗性前立腺癌 / 3Dオルガノイド / 神経内分泌癌 / YAP / ARHGAP29 / 前立腺癌 / バイオマーカー / ARHGAP18 / ３Ｄオルガノイド / リキッドバイオプシー / 薬剤選択マーカー |
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| Outline of Final Research Achievements |
We will continue to establish passage technology and functional analysis for preparation of 3D organoids from prostate cancer specimens.
In addition, immunostaining of YAP and ARHGAP29 showed significant correlation with clinical factors, pathological factors and prognosis using specimens of radical prostatectomy. In cell line analysis, expression of ARHGAP29 downstream of YAP is predominantly upregulated in PC3 and significantly downregulated in LNCaP, and knocking down ARHGAP29 in PC3 significantly suppresses cell proliferation and reduces invasiveness. And phosphorylation of YAP was promoted. Conversely, over-expression of ARHGAP29 in LNCaP promoted cell proliferation and significantly enhanced infiltration ability. Moreover, the phosphorylation of Cofilin was increased by knockdown of ARHGAP29 in PC3 and the mechanism of acquisition of malignant traits via the YAP-ARHGAP29-Cofilin pathway was elucidated in prostate cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により特にホルモン非依存性前立腺癌においてYAP-ARHGAP29経路の悪性形質獲得へのメカニズムの一端が解明され、それらが新たな前立腺癌の悪性度や予後を予測するバイオマーカーとなる可能性が示唆された。またYAPやARHGAP29をターゲットとした創薬開発は去勢抵抗性前立腺癌の新たな治療戦略となる可能性があり、社会的意義は十分に高いものと思われる。
今後3Dオルガノイドを用いた解明がさらに加われば、動物実験を回避し、直接個人でのオーダーメイド医療に道が開けると思われ、臨床的意義は極めて高い。
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